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Efficacy and Safety of Tideglusib in Congenital Myotonic Dystrophy

Phase 2
Completed
Conditions
Congenital Myotonic Dystrophy
Interventions
Drug: Placebo
Registration Number
NCT03692312
Lead Sponsor
AMO Pharma Limited
Brief Summary

This is a randomized, multicenter, double-blind, placebo-controlled, Phase 2/3 study of patients (aged 6 to 16 years) diagnosed with Congenital Myotonic Dystrophy (Congenital DM1).

Detailed Description

This is a randomized, double-blind, placebo controlled study of weight adjusted dose 1000 mg/day tideglusib versus placebo in the treatment of children and adolescents 6-16 years of age with Congenital DM1.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
56
Inclusion Criteria
  1. Male or female children and adolescents aged ≥6 years and ≤16 years

  2. Diagnosis of Congenital DM1 (also known as Steinert's disease)

    • Diagnosis must be genetically confirmed

    • One or more of the following clinically relevant (e.g. requiring medical intervention) signs or symptoms was evident within the first month after birth:

      • Hypotonia
      • Generalized weakness
      • Respiratory insufficiency
      • Feeding difficulties
      • Clubfoot or another musculoskeletal deformity
  3. Subject must be able to walk and complete the 10-meter walk-run test (orthotics/splints allowed, forearm crutches are not allowed)

  4. Written, voluntary informed consent must be obtained before any study related procedures are conducted.

    • Where a parent or LAR provides consent, there must also be assent from the subject
  5. Subject's caregiver must be willing and able to support participation for duration of study

  6. Subject must be willing and able to comply with the required food intake restrictions as outlined per protocol

Exclusion Criteria
  1. Not able to walk; (full time wheel chair use)
  2. Body mass index (BMI) less than 13.5 kg/m² or greater than 40 kg/m²
  3. New or change in medications/therapies within 4 weeks prior to Screening
  4. Use of strong CYP3A4 inhibitors (e.g clarithromycin, telithromycin, ketoconazole, itraconazole, posaconazole, nefazodone, idinavir and ritonavir) within 4 weeks prior to Baseline
  5. Concurrent use of drugs metabolized by CYP3A4 with a narrow therapeutic window (e.g. warfarin and digitoxin)
  6. Current enrollment in a clinical trial of an investigational drug or enrollment in a clinical trial of an investigational drug in the last 6 months
  7. Existing or historical medical conditions or complications (e.g. neurological, cardiovascular, renal, hepatic, endocrine, gastrointestinal or respiratory disease) which would cause the investigator to conclude that the subject will not be able to perform the study procedures or assessments or would confound interpretation of data obtained during assessment
  8. Hypersensitivity to tideglusib and its excipients including allergy to strawberry

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
TideglusibTideglusibWeight adjusted tideglusib, orally, once daily
TideglusibPlaceboWeight adjusted tideglusib, orally, once daily
PlaceboPlaceboMatching placebo, orally, once daily
Primary Outcome Measures
NameTimeMethod
Change in Clinician-Completed Congenital DM1 Rating Scale (CDM1-RS)22 weeks

The Clinician-Completed Congenital DM1 Scale is an 11-item rating scale completed by the clinician that scores the symptom severity of domains that are clinically relevant in Congenital DM1.

Secondary Outcome Measures
NameTimeMethod
Change in Clinical Global Impression- Improvement Scale (CGI-I) scores22 weeks

The clinician administered CGI-I rates how much the subject's illness has improved or worsened relative to a baseline state.

Change in Top 3 Caregiver Concerns Visual Analogue Scale (VAS) score22 Weeks

The Top 3 concerns VAS allows caregivers to identify their main three causes of concern, related to the subject's myotonic dystrophy, rather than these being pre-specified within a scale and then rating how these concerns have changed at specific time-points during the study.

Caregiver Completed Congenital DM1 Rating Scale (CC-CDM1-RS)22 weeks

The Caregiver-Completed Congenital DM1 Scale is a caregiver assessment of the subject on symptoms that may occur in individuals with CDM1. There are a total of 11 clinically relevant symptoms that the caregiver is asked to rate the severity of.

Clinical Global Impression - Severity Scale (CGI-S)22 weeks

The Clinical Global Impression - Severity Scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the subject's illness at the time of assessment, relative to the clinician's past experience with subjects who have the same diagnosis.

10-meter walk-run test22 weeks

The 10-meter walk/run test is a performance measure used to assess walking speed in meters per second over a short distance. It can be used as an assessment of functional mobility.

Incidence of Adverse events (AEs), including serious adverse events (SAEs), between Screening to end of study.22 to 28 weeks

Adverse events may be volunteered spontaneously by the subject, or discovered as a result of general, non-leading questioning by physician.

Incidence of abnormal findings in objective assessments (e.g. laboratory values, ECGs, vital signs and bone mineral density) between Screening and end of study.22 to 28 weeks

Abnormal laboratory findings (e.g. hematology, liver function, biochemistry, urinalysis) or other abnormal assessments (e.g. ECGs, vital signs) that are judged by the Investigator as clinically significant will be recorded as AEs or SAEs if they meet the definition of an AE. The Investigator will exercise his or her medical and scientific judgment in deciding whether an abnormal laboratory finding or other abnormal assessment is clinically significant.

Trial Locations

Locations (14)

The Bright Alliance

🇦🇺

Randwick, New South Wales, Australia

University of Utah Hospital

🇺🇸

Salt Lake City, Utah, United States

New Zealand Clinical Research (NZCR)

🇳🇿

Auckland, New Zealand

Newcastle University

🇬🇧

Newcastle Upon Tyne, United Kingdom

University of Rochester Medical Center

🇺🇸

Rochester, New York, United States

Arkansas Children's Hospital

🇺🇸

Little Rock, Arkansas, United States

University of California, Los Angeles (UCLA)

🇺🇸

Los Angeles, California, United States

Stanford University

🇺🇸

Palo Alto, California, United States

University of Iowa Hospitals and Clinics

🇺🇸

Iowa City, Iowa, United States

Ann & Robert H. Lurie Children's Hospital of Chicago

🇺🇸

Chicago, Illinois, United States

University of Pittsburgh Medical Center

🇺🇸

Pittsburgh, Pennsylvania, United States

Virginia Commonwealth University - Department of Neurology. Muscular Dystrophy Translational Research Program.

🇺🇸

Richmond, Virginia, United States

Children's Hospital London Health Sciences Centre (LHSC)

🇨🇦

London, Ontario, Canada

Children's Hospital of Eastern Ontario

🇨🇦

Ottawa, Ontario, Canada

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